Pneumonia in children is a major cause of morbidity and mortality worldwide and the leading cause of death in children younger than 5 years of age worldwide. Among children in the United States, pneumonia and influenza are the eighth leading causes of death. Although the burden of pneumonia in children is well appreciated, recent data on the incidence and etiology of pneumonia in children are few. Moreover, the epidemiology of childhood pneumonia is changing due to the impact of Haemophilus influenzae type b (Hib) vaccine and pneumococcal conjugate vaccine, and the emergence of non-vaccine serotypes of Streptococcus pneumioniae and highly virulent clones of methcillin resistant Staphylococcus aureus (MRSA). Several respiratory viruses have been recognized in recent years, and there is increased recognition of the impact of influenza in causing primary pneumonia as well as life-threatening secondary infections. Determining the true etiology of pneumonia has been difficult. The primary reasons for this are: 1) the large number of bacterial and viral agents that may cause pneumonia;2) the frequency of viral and bacterial co- infections;3) the limited availability of deep respiratory specimens from children;4) the limitations of current laboratory technology;and 5) antibiotic therapy initiated before microbiological evaluation. These limitations result in empirical clinical management of children with pneumonia. The optimum management of pediatric pneumonia is dependent on understanding the epidemiology of the pathogens that cause pneumonia by age and geographic region. The University of Utah, in collaboration with the Associated and Regional University Pathologists Laboratories and Research Enterprise, as well as Idaho Technology, Inc., is uniquely suited to address this problem. We have been performing population-based studies of respiratory infections in Salt Lake County, a region with one of the highest birth rates in the US, have outstanding information technology resources, and have extensive experience with standard and novel molecular diagnostic tests. The Specific Aims of this proposal are: Specific Aim 1: Identify all children (1 week to 18 years of age) residing in Salt Lake County hospitalized for clinically diagnosed and radiologically-confirmed, community-acquired pneumonia. Enroll all children meeting a strict case definition (estimated number >500/year) into a prospective clinical study to determine the incidence, etiology and outcomes of pneumonia among hospitalized children, using state of the art diagnostic methods. Specific Aim 2: Determine the incidence, etiology and outcomes of pediatric influenza-associated pneumonia in Salt Lake County, including primary viral pneumonia, viral and bacterial co-infection, and post-influenza bacterial pneumonia. Specific Aim 3: Document the etiology of pediatric pneumonia due to established and emerging pathogens using molecular analysis and a novel diagnostic platform. a. Improve the ability to identify the etiology of presumed bacterial infection using molecular analysis of pleural fluid and blood. b. Expand the range of pathogens evaluated as potential causes of hospitalized pediatric pneumonia to include emerging viruses such as non-SARS coronaviruses, parainfluenza virus 4 (PIV 4) human metapneumovirus, rhinoviruses, and bocavirus. The successful achievement of these Specific Aims will allow us to determine the incidence and etiology of pediatric hospitalized pneumonia and to further understand the complications associated with influenza. PUBLIC HEALTH RELEVANCE: Our study, Epidemiology and Etiology of Hospitalized Pneumonia in Children, supports and addresses the National Center for Immunization and Respiratory Diseases (NCIRD) of CDC objectives of "Healthy People 2010" to prevent disease, disability, and death from infectious diseases, including vaccine-preventable diseases to protect Americans from infectious diseases. It will lead to improved understanding of the spectrum of viruses and bacteria responsible for pneumonia will aid in appropriate choices of antimicrobial therapy. Understanding the frequency and etiology of bacterial infections following influenza will aid in pandemic planning. The data obtained from the proposed studies will be vital for evidence-based management of pneumonia in children.